1979 Volume 4 Issue 2 Pages 87-98
Accumulation of fluphenazine enanthate (FE) and fluphenazine decanoate (FD), long-acting neuroleptic durgs, after repeated administration was investigated by means of their inhibitory effect on the discriminated avoidance response in rats. When FE 0.13 mg/kg, and FD 0.13 and 0.25 mg/kg were given i.m. once a day, the inhibitory effect enhanced progressively until about the 10th and 30th day in the cases of FE and FD, respectively. The maximum levels of suppression were maintained during the later medication periods. After the withdrawal of the drugs, the avoidance response recovered gradually and returned to each pre-drugged level on about the 20th, 30th and 100th day in the cases of FE 0.13, FD 0.13 and FD 0.25 mg/kg/day, respectively. When 1 and 2 mg/kg of each FE and FD were given i.m. once a week for 8 weeks, a progressive enhancement of the avoidance-suppressing effect was observed until the 3rd and 6th injection in the cases of FE and FD, respectively, and thereafter almost the same weekly variation pattern of the avoidance response was repeated. The present results suggest that the enhancement of the avoidance-suppressing effect after repeated administration of FE and FD is resulted from the accumulation of these drugs, and that the absorption and metabo1ism of the drugs in the body reach a steady state after 10-15 days in the former and 30-35 days in the latter, independently of the dose and administration intervals.
